Archive for the ‘Origins of Life’ Category

Yesterday, Science magazine published what are effectively two death certificates for arsenic life (12). These twin papers delve back into the experiments first conducted on the GFAJ-1 bacterium that led Felisa Wolfe-Simon and coworkers to conclude that this organism can grow using arsenic instead of phosphorus.

In the newest reports, Redfield and coworkers were more fastidious than FWS in their experimentation and reported that the presence of arsenate did not affect the growth of the bacterium when phosphate was limiting. They also found no covalently incorporated As in the DNA of GFAJ-1. Erb, et al. found similar results. You can read the papers for yourselves, but suffice it to say that these are findings that jive with everything we know about biochemistry excluding the one paper published by Wolfe-Simon. The only reasonable analysis is that until bona fide experimental evidence to the contrary is presented, there are no organisms we know of that can function by substituting As for P in their DNA.

To follow up on one of my earlier posts, unfortunately, Felisa Wolfe-Simon *still* does not get it. The first rule of getting out of a hole is to stop digging. Giving a statement like the following to USA Today does not help FWS’s cause:

The “new research shows that GFAJ-1 does not break the long-held rules of life,” says the editorial statement by Science. The bacteria, “is likely adept at scavenging phosphate under harsh conditions, which would help to explain why it can grow even when arsenic is present within the cells,” it says.

Wolfe-Simon says in response, “There is nothing in the data of these new papers that contradicts our published data.” Her team hopes to submit more data on the microbe for publication within a few months, she suggests.

Her latest collaborator also decided to pick up a shovel in commenting to the Washington Post:

Wolfe-Simon, now on a NASA fellowship at the Lawrence Berkeley National Laboratory, is collaborating with senior scientist John A. Tainer on wide-ranging studies of the bacterium. In an interview Saturday, Wolfe-Simon and Tainer said that they had produced tentative results in the Berkeley lab almost identical to the original results at a U.S. Geological Survey laboratory, and that they were busy finishing the research and preparing another paper.

Tainer said the two new studies in Science may have come to different results than theirs because of the methodologies used, the precision used to detect arsenates and the provenance of the cells. He said the authors of the two new papers “may well regret some of their statements” in the future.

“There are many reasons not to find things — I don’t find my keys some mornings,” he said. “That doesn’t mean they don’t exist. The absence of a finding is not definitive.”

Wolfe-Simon and her numerous collaborators had made samples of GFAJ-1 broadly available after her initial results caused a storm of controversy, but she and Tainer said they may have been contaminated or modified in transit.

Even the Catholic Church admitted it was wrong when faced with the overwhelming evidence that the Sun does not revolve around the Earth. And we’ve just discussed scientific megablunders with regard to Ronald Breslow and the space dinosaurs paper: when you are spectacularly wrong, you need to admit it for people to let you move on. Denying or ignoring your mistakes prolongs the story.

The second rule of getting yourself out of a hole is to grab a life-line if someone offers you one. Wolfe-Simon could have easily jumped on the “good news” of the GFAJ-1 story by embracing the bacterium’s remarkable resistance to arsenic—which was verified. Instead, it appears as though FWS has doubled down behind the initial report. I’ll keep an open mind when she presents her newest results, but I don’t expect much.

As an aside, it is interesting to note that Science (with a capital “S”) got dragged through the mud again. As if publishing the flawed initial report wasn’t bad enough, the magazine was forced to publish the Redfield and Erb papers prematurely because Redfield broke the embargo on her own paper at a decided to present the results yesterday at a popular conference on evolution. What a mess for Science!

JACS has removed Ronald Breslow’s “Space Dinosaur” paper from its Web site. Users who click to view the PDF are greeted with the following message:

10.1021/ja3012897
This article was removed by the publisher due to possible copyright concerns. The Journal’s Editor is following established procedure to determine whether a violation of ACS Ethical Guidelines to Publication of Chemical Research has occurred.

This is an interesting move by the editors. While the paper has not yet appeared in print, its presence on the ASAP site constitutes “official” publication. There is something unwholesome about making the paper vanish. After all, isn’t that why we have addition/correction notices? Otherwise, why wouldn’t we go just into the original documents and change them?

Update (9:05 PM) — The guide “Notice to Authors of JACS Manuscripts” verifies that the ASAP version constitutes official publication of the paper:

Authors must consider that the publication date for a paper is the date of first disclosure, either the Just Accepted date, ASAP date, or date on which the issue is posted on the web.

The Breslow “dinosaur” story has intensified to a crescendo. What started as bewilderment over a silly press release issued by the ACS about an otherwise unremarkable paper, has morphed into serious accusations of misconduct in the form of self-plagiarism by a living legend of chemistry. The conversation has transpired almost completely on chemistry blogs and microblogs (e.g., Twitter). In an effort to keep track of everything, I have collected a list of pertinent links below, which I plan to curate as the story evolves.

It seems that once again, the collective chemical Internet has uncovered a serious case of misbehavior in our field. This amateur journalism was a truly distributed effort, with multiple sites contributing new facts and insights, and with each site building on the work of the others. The cooperation and openness of the system are two of the reasons I value blogs and blogging. It is heartening to see that small groups of people can catalyze positive change by drawing attention to obvious problems and stimulating thoughtful analysis.

27/4/2012 – C&EN – “Breslow Paper in JACS Questioned” – Editor-in-chief of C&E News reports on the pulled paper in the official newsmagazine of the American Chemical Society. The article was updated on 30/4/2012 with a comment from Breslow.

The “Space Dinosaur” paper by Ronald Breslow of Columbia University continues to attract negative attention (12), and it does so because the American Chemical Society continues to mishandle the situation on two levels. The first set of problems centers on the press release issued by the ACS Press Room, while the second set concerns JACS and the ethical publication of research. Both sets of problems have obvious solutions, but these solutions require courageous action from an organization that, to many of its members, appears bereft of courage and reason.

Problem #1: The Dinosaur Press Release

We previously analyzed Breslow’s homochirality paper in JACS and its accompanying press release. The content of the paper was interesting, but the press release missed the point. Perhaps in an effort to engage a wider audience, the Press Room ran with a fanciful, poetic thought on dinosaurs that appeared at the close of the paper. In the process, they almost completely ignored the crux of Breslow’s scientific work. I am not alone in this analysis; the release was instantly ridiculed on Twitter and on many chemistry blogs, yet the ACS Press Room left the story on its front page and in its PressPac for a full week. While some news reports recognized the situation for what it is (123), other news outlets have run with the release (12345), and as a result, are perpetuating the bizarre idea.

Solution #1: Issue an Updated Press Release and Draw Attention to It

The ACS must strive to communicate science accurately to the public and in a manner consistent with the spirit of the research. Breslow’s paper had little—if anything—to do with dinosaurs. The press release was an absolute farce. To not correct the focus of the release and allow it to snowball in the mainstream press is completely antithetical to one of the fundamental purposes of the ACS as outlined in its National Charter: “to foster public welfare and education.”

The ACS Press Room must pull the original release, issue a corrected version, and forward it to all news organizations that picked up the story. Furthermore, an employee should be assigned the task of posting links to the updated release in the comment threads for any news stories on the Internet where a corresponding comment threads also exists.

A certain degree of courage is required to publicly acknowledge a mistake, and even more is required to step boldly into the light and attempt to repair any damage that was caused. It is much, much easier to hide, do nothing, and wait for the story to die down. But while it is a thankless task, our society has a duty to spend a day fixing this damage before it moves on.

Problem #2: Ethical Concerns Regarding the Paper in JACS

It has been noted on Twitter—as well as in comment threads here, on See Arr Oh’s blog, and Chemistry-Blog—that it appears that large portions of Breslow’s paper in JACS have been self-plagiarized from not one, but two previously published papers (12). The most thorough analysis was conducted by Stu from Nature Chemistry, where he took a pen to the Breslow paper and highlighted the portions that were lifted “>97-98% verbatim from” the previous publications. The five pages of Breslow’s perspective are COVERED in ink (123). [These three photos are a must-see. Incidentally, I highly recommend following @stuartcantrill‘s Twitter feed.]

Some commenters have asked whether self-plagiarism is that big of a deal. I can see tenable arguments for either side of this question, and in cases where this is true, it makes sense that any journal should be allowed to set its own policy. The policy for JACS is stated in the ACS Ethical Guidelines to Publication of Chemical Research:

Authors should not engage in self-plagiarism (also known as duplicate publication) – unacceptably close replication of the author’s own previously published text or results without acknowledgement of the source. ACS applies a “reasonable person” standard when deciding whether a submission constitutes self-plagiarism/duplicate publication. If one or two identical sentences previously published by an author appear in a subsequent work by the same author, this is unlikely to be regarded as duplicate publication. Material quoted verbatim from the author’s previously published work must be placed in quotation marks. In contrast, it is unacceptable for an author to include significant verbatim or near-verbatim portions of his/her own work, or to depict his/her previously published results or methodology as new, without acknowledging the source.

Note that this policy makes no distinction among articles, communications, and perspectives, so it should be assumed to apply to any publication in JACS. Furthermore, it is clear from the format and tone of Breslow’s manuscript that it was intended to be a “proper” report of research rather than an essay. The “perspective” label can offer no wiggle room here. To me, the paper seems like a textbook case of self-plagiarism.

Solution #2: Retract the Paper

Ronald Breslow is a powerful member of the chemical elite, and he has led a distinguished career associated with a strong body of research. He has achieved the rank of University Professor, won the highest honor of the American Chemical Society, and even served as the President of our Society. But no scientist should be above the rules. The unfortunate duty of Peter Stang, the editor-in-chief of JACS, is clear. He must:

(1) Delay the publication of Breslow’s paper in print. It is unfortunate that the paper has been published, but unless the originality of the paper is verified, it must be held in limbo as an ASAP.

(3) Force the retraction of the manuscript and make a public notice of doing so.

(4) Sanction Breslow, privately, by suspending him from publishing in JACS for a period of at least one year.

No person would relish taking these steps, especially against someone who wields the power and influence of a man like Ronald Breslow. But to take no action would make an absolute mockery of the ethics of publication in ACS journals. Stang must summon the courage to protect the integrity of our field’s flagship journal; the situation demands it.

You all know that origin-of-life research is near and dear to my heart, and you’re probably sick of how often I lament that the problem has not taken root in chemical academia despite the fact that it almost certainly requires a chemical solution. One of the few PIs at a top university who has dabbled in the field is Ronald Breslow, University Professor at Columbia and a past president of the ACS. Breslow just published this little diddy as a perspective in JACS:

First of all, how often do you see a single-author paper in JACS anymore? It is kind of refreshing. It also means that you can attribute 100% of the content to Breslow, including the ChemDraw structures:

What the hell is that? If I drew that structure on a slide in grad school, my committee would have eviscerated me.

Anyway, let’s get down to the science. Breslow’s premise is that you can take alpha-methyl amino acids found in non-racemic mixtures in meteorites—generated by selective destruction of one enantiomer by circularly polarized UV light—and “use” these compounds to generate non-racemic mixtures of sugars (which are also found as moieties in nucleic acids). Since meteors hit the early Earth with great frequency, maybe one or more of these chiral amino acids was the origin of life’s homochirality. It is an interesting idea and one worth keeping in mind. We could argue all day about how unlikely the scenario is, but this field needs to collect more neat ideas accompanied by simple demonstrations. That said, I take issue with the premise of the paper as outlined in the Introduction:

In 1969 a carbonaceous chondritic meteorite landed in Murchison Australia carrying many organic compounds. These compounds were apparently able to survive the frictional heating as the meteorite passed through our atmosphere since they were initially at ca. 10K, and chondritic meteorites are pieces of rock, with low thermal conductivity, from the asteroid belts that surround the sun. When the meteorite was split open the interior was still cold enough to freeze water.

Among the compounds identified were the amino acids alanine, valine, aspartic acid, glutamic acid, proline, and leucine, which were racemic, with equal mixtures of the L and D forms, along with achiral glycine. However, five amino acids were found that had methyl groups instead of hydrogens on their alpha positions (Figure 1), and these had a range of small excesses of the enantiomers originally described as the L amino acids (in modern terminology they are the S enantiomers). Since that time, these and other α‐methyl amino acids with small excesses of the S enantiomer have been found in the Murchison, Murray, and Orgueil meteorites (ref 1).

The whole point of why the Murchison meteorite is so interesting is that while the “natural” amino acids in it were initially thought to be racemic, subsequent analyses revealed them to have enantiomeric excesses. I could be missing more recent analyses, but I don’t think so. Breslow should check out these seminal papers (12) and revise his background before the paper is “truly” published in JACS.

It is things like the odd ChemDraw structures and completely wrong information in the background that make me question the quality of peer review in JACS (and in all of chemistry, for that matter). I think one should also question the fairness of the editors, for I cannot imagine that this paper would have made it anywhere near publication in JACS if the author were Assistant Professor Joe Schmoe from Sunny Valley Technical College. But that said, the editors of JACS are the sole arbiters of what is “worthy” of publication in JACS, so I’ll just accept it and move on.

Normally, I wouldn’t blog about an otherwise run-of-the-mill paper about the origin of life, but this paper has really taken off in the world of popular science thanks to what amounts to a poetic thought by Breslow used to close the paper:

An implication from this work is that elsewhere in the universe there could be life forms based on D amino acids and L sugars, depending on the chirality of circular polarized light in that sector of the universe or whatever other process operated to favor the L α‐methyl amino acids in the meteorites that have landed on Earth. Such life forms could well be advanced versions of dinosaurs, if mammals did not have the good fortune to have the dinosaurs wiped out by an asteroidal collision, as on Earth. We would be better off not meeting them.

Since you are a reader of blogs, you will recognize this paragraph for what it is: a silly piece of fluff meant to close an otherwise esoteric piece on a humorous note. I’ve got no problem with that. We can argue over whether the joke is funny, but the attempt at humor is obvious…

…except to the staff in the ACS Pressroom, for they issued the following press release to promote the paper. I am copying it here verbatim because these things are intended for distribution—and because it is ridiculous.

Could “advanced” dinosaurs rule other planets?

New scientific research raises the possibility that advanced versions of T. rex and other dinosaurs — monstrous creatures with the intelligence and cunning of humans — may be the life forms that evolved on other planets in the universe. “We would be better off not meeting them,” concludes the study, which appears in the Journal of the American Chemical Society.

In the report, noted scientist Ronald Breslow, Ph.D., discusses the century-old mystery of why the building blocks of terrestrial amino acids (which make up proteins), sugars, and the genetic materials DNA and RNA exist mainly in one orientation or shape. There are two possible orientations, left and right, which mirror each other in the same way as hands. This is known as “chirality.” In order for life to arise, proteins, for instance, must contain only one chiral form of amino acids, left or right. With the exception of a few bacteria, amino acids in all life on Earth have the left-handed orientation. Most sugars have a right-handed orientation. How did that so-called homochirality, the predominance of one chiral form, happen?

Breslow describes evidence supporting the idea that the unusual amino acids carried to a lifeless Earth by meteorites about 4 billion years ago set the pattern for normal amino acids with the L-geometry, the kind in terrestial proteins, and how those could lead to D-sugars of the kind in DNA.

“Of course,” Breslow says, “showing that it could have happened this way is not the same as showing that it did.” He adds: “An implication from this work is that elsewhere in the universe there could be life forms based on D-amino acids and L-sugars. Such life forms could well be advanced versions of dinosaurs, if mammals did not have the good fortune to have the dinosaurs wiped out by an asteroidal collision, as on Earth. We would be better off not meeting them.”

What. The. Hell. Some booger-eating PR guy on 16th Street jumped to the end of the manuscript and took Breslow’s joke at face value. Then, his/her editor never thought to question the idea, and sent the press release out in the weekly PressPac. Now, the ACS is the laughing stock of the world of scientific publishing and popular science writing.

I guess we’ve learned nothing from the NASA/Wolfe-Simon/Arsenic Life episode. Why the hell do these things always seem to happen to origin-of-life chemistry?

I was saddened to learn of the recent death of Robert Shapiro, Professor Emeritus of chemistry at New York University. Although I went to NYU and essentially lived in the chemistry department, I cannot recall meeting him in my time as an undergrad. It’s a shame, because he was one of the few professors in the field of origin-of-life chemistry—my favorite subject of research.

I continue to be amazed that OoL research is not more popular among chemists. The mystery of how life originated on Earth roughly four billion years ago has got to be the greatest question in our planet’s history, and the answer all but certainly falls within the exclusive purview of chemistry—physics is too impractical to solve the problem, and by the time you get to biology, the problem has long since been solved.

Shapiro wrote what is by far my favorite book about the origin of life, Origins: A Skeptic’s Guide to the Creation of Life on Earth. When people ask me what book they should read to get a taste of the problem, I tell them that just about any popular book on the subject is a fine first read, but they should be sure to read Shapiro’s book next. I think it’s best to get a taste of the romanticism of the field and listen to the proponents’ sales pitches for the main theories before experiencing how Shapiro tears them apart. Origins is a bucket of cold water best tossed on someone after a long, warm shower—it stings, but it is also invigorating.

I was glad to finally meet Shapiro when he visited Harvard to give a talk in 2008. True to form, he delivered a lecture poo-pooing the idea that RNA or DNA could have been important in the origin of life—a gutsy prospect considering RNA-OoL proponent (and eventual Nobel laureate) Jack Szostak was at Harvard and sure to be in the audience. But that’s the thing I loved about Shapiro—he seemed to live to identify problematic ideas and call them out with vigor. As more and more chemists join the ranks of those who oversell their work, I think that it’s great when respected chemists stand up and share their skepticism about the value of an idea, discovery, or line of research. While many professors are happy to grumble in private, very few are willing to criticize their colleagues publicly.